The Final Four consisted of Connecticut, making their first ever Final Four appearance; Ohio State, making their ninth Final Four appearance and first since 1968; Michigan State, making their third Final Four appearance and first since their 1979 national championship; and Duke, the overall number one seed and making their first Final Four appearance since losing the national championship game in 1994.

In the national championship game, Connecticut defeated Duke 77-74 to win their first ever national championship, snapping Duke's 32-game winning streak, and scoring the biggest point-spread upset in Championship Game history. Duke nonetheless tied the record for most games won during a single season, with 37, which they co-held until Kentucky's 38-win seasons in 2011–12 and 2014–15. The 2007–08 Memphis team actually broke this record first, but the team was later forced to forfeit their entire season due to eligibility issues surrounding the team.

Richard "Rip" Hamilton of Connecticut was named the tournament's Most Outstanding Player. This was a significant victory for the program, as it cemented Connecticut's reputation as a true basketball power after decades of barely missing the Final Four. Also, the Huskies were the last men's national champion to date that did not play football at the level now known as the Football Bowl Subdivision (known as Division I-A from 1978 to 2006) at the time of their title. Connecticut then played football in Division I-AA, now the Football Championship Subdivision; by the time of the Huskies' next men's basketball title in 2004, the school's football team had upgraded to the current FBS level.

This tournament is also historically notable as the coming-out party for Gonzaga as a rising mid-major power. The Bulldogs became the nation's basketball darlings during a run to the West Regional final in which they defeated three major-conference powers, including 1998 Final Four participant Stanford, and took UConn literally to the last minute before losing. Gonzaga has made every NCAA tournament since then, and is now generally considered to be a high-major program despite its mid-major conference affiliation.

Due to violations committed by Ohio State head coach Jim O'Brien, the Buckeyes were forced to vacate their appearance in the 1999 Final Four.[1]

St. Petersburg became the 27th host city, and Tropicana Field the 32nd host venue, for the Final Four. Tropicana Field, the home of baseball's Tampa Bay Devil Rays, was the sixth different domed stadium to host a Final Four, though given its inability to be converted to a center court arena, it is unlikely to host one again. There were four new venues in the 1999 tournament, two in completely new host cities for the tournament. For the first time, the tournament came to Boston at the FleetCenter, which had replaced the Boston Garden in 1995. Despite the original Garden's rich college and NBA history, it never had hosted any NCAA tournament games. The tournament also came to downtown Phoenix for the first time, at the NBA home of the Phoenix Suns. Previous games in the metropolitan area were played in suburban Tempe at Arizona State University. For the second straight year, the Midwest Regional games were held in a new venue in St. Louis, this time at the Trans World Dome, then home to the NFL's St. Louis Rams. The tournament also returned to Seattle, this time at KeyArena, the downtown home to the Seattle SuperSonics. This tournament would be the last held at McNichols Sports Arena, which was scheduled to close later in the year and is now the site of parking for Sports Authority Field at Mile High; subsequent games in Denver have moved to the Pepsi Center. It is also the last tournament to date to include Tropicana Field and Thompson–Boling Arena, as neither has hosted since.

Despite their loss in the finals to Connecticut, the 1998–1999 Duke team won 37 games.[2] This tied them with Duke's 1985–86 team, UNLV's 1986–87 squad, and later, Illinois' 2004–05 team and Kansas's 2007–08 team, for the most wins in a season, until their record was broken by the 38-win Memphis team in 2007–08. However, as the NCAA vacated Memphis' 2007–2008 season due to the ineligibility of Derrick Rose, they reclaimed the 37-win record. The mark would once again be raised to 38 wins after Kentucky's dominant title run in 2012, which then tied with Kentucky's 2014–15 team. Interestingly, only one of the first 5 teams to be the winningest single-season teams won a national championship; UNLV's squad lost in the national semifinal to Indiana, and the other teams lost in the finals, to Louisville, UConn, and North Carolina, while Kansas defeated Memphis in the 2008 national championship game. Kentucky's 2014–15 squad suffered their only loss that season in the national semifinal to Wisconsin.

Connecticut's victory in the finals marks the biggest upset in Championship Game history in the NCAA Tournament, as they were 9.5-point underdogs in the contest despite having compiled a 33-2 record going into the Championship game, including a 14-2 record in the tough Big East Conference. In fact, Connecticut had spent more weeks as the number 1 team in the country, according to the AP Top 25 Poll, than had Duke. The previous record was held by Villanova, who defeated Georgetown as 9-point underdogs in 1985.[3]

The 1999 Final Four would be the last time Tropicana Field would host NCAA tournament games. For Duke, they had 2 straight promising seasons end on the Tropicana Field floor, with a 86-84 loss to Kentucky in the 1998 South Regional final, and then the 1999 National Championship game.